B cell development, autoimmunity and immune regulation

B 细胞发育、自身免疫和免疫调节

• 批准号: MR/Y033701/1
• 负责人: Richard Cornall
• 金额: $ 238.38万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY033701%2F1
• 关键词: cell; development; autoimmunity; immune; regulation

Our goal is to understand how the immune system regulates the response to self- and foreign antigens, including how B cells are selected during their development and ontogeny, the causes of human immunodeficiency and how insights from these can help us to improve the normal immune response to antigens, and how dysregulation of the immune response leads to systemic autoimmune disease. We have a longstanding interest in how checkpoint receptor agonists may be used to suppress inflammation and autoimmune disease in humans. More recently, we have started to investigate the immune pathology of lupus and other autoimmune kidney diseases, to improve diagnosis and stratify patients, and test new therapeutic targets. We address these questions with a variety of functional, genetic and therapeutic approaches. Our experiments use transgenic mice, molecular tools and models that can be used to track cells and characterise the immune response to antigens, self-tolerance and B cell selection. We use gene targeting to model human disease and gain insights into new mechanisms, and we are developing single-cell approaches, including spatial imaging, to characterise the immune response and the pathology of disease. We have formed a university spin-out company, MIROBIO, to translate our discoveries into clinical practice.

我们的目标是了解免疫系统如何调节对自身和外来抗原的反应，包括 B 细胞在发育和个体发育过程中如何选择、人类免疫缺陷的原因以及从中获得的见解如何帮助我们改善正常的免疫反应抗原，以及免疫反应失调如何导致系统性自身免疫性疾病。我们长期以来对如何使用检查点受体激动剂来抑制人类炎症和自身免疫性疾病感兴趣。最近，我们开始研究狼疮和其他自身免疫性肾脏疾病的免疫病理学，以改进诊断和对患者进行分层，并测试新的治疗靶点。我们通过各种功能、遗传和治疗方法来解决这些问题。我们的实验使用转基因小鼠、分子工具和模型，可用于追踪细胞并表征对抗原的免疫反应、自我耐受和 B 细胞选择。我们使用基因靶向来模拟人类疾病并深入了解新机制，并且我们正在开发单细胞方法（包括空间成像）来表征免疫反应和疾病病理学。我们成立了一家大学衍生公司 MIROBIO，将我们的发现转化为临床实践。